Tech Chemists Publish Ground-Breaking Work On Two-Color Dyes

SOCORRO, N.M. August 28, 2009 – New Mexico Tech chemistry professor Dr. Michael Heagy has been making headlines for his work with dual fluorescent dyes in recent weeks.

Chemical Communications reported about Heagy’s work in early August. That report was then summarized in Highlights in Chemical Science. Both journals are published by the Royal Society of Chemistry, the largest organization in Europe for advancing the chemical sciences.

“We’re kind of excited about this publicity,” Heagy said. “We’ve been involved in fluorescent dyes for a while. We published a fairly significant paper about five years ago, but this sort of recognition is exciting.”

Heagy and three graduate students published the paper, “Discovery of Dual Fluorescent 1,8 Naphthalimide Dyes Based On Balanced Seesaw Photophysical Model,” in Chemical Communications in August. The student scientists include leading author Prem Nandhikonda, a doctoral student; Dr. Michael Begaye, who graduated from Tech in May 2008; and Zhi Cao, who earned his master’s at Tech in December 2008.

Dr. Micheal Heagy (right) and Prem Nandhikonda illustrate the seesaw analogy of dual-fluorescent dyes -- complete with different color T-shirts. Heagy represents the excited state of a molecule, while Nandhikonda represents the opposite state.

Heagy’s group is doing groundbreaking work in identifying patterns that characterize dual fluorescent dyes. Most fluorescent dyes emit one color. Heagy is finding predictors that will help chemists create new dyes that emit two colors.

For the article in Highlights, Heagy was quoted as saying, “Just as green and red traffic signals convey far more information to a motorist than a single yellow caution flasher, so also is the greater information obtained from dyes that emit in two colors. … The ability to obtain two colors from an organic dye improves biological analyses by providing a second signal or output to monitor.”

Heagy first stumbled upon a dual fluorescent dye in 2003, quite by accident.

“It was an anomalous finding,” he said. “The initial discovery of dual fluorescent dyes was made 30 years ago, but I was unaware of that. After we discovered one, we’ve been pursuing others ever since. I learned years ago from my Ph.D. advisor, Nobel Laureate George Olah, that the anomalies in science usually make the most interesting pursuits."

Heagy published a paper in Organic Letters in 2004 about his initial findings. That paper has been cited more than 60 times already.

After that initial publication, Heagy and his students synthesized 42 compounds in an attempt to find a pattern, finding five dyes with dual fluorescent. In Heagy’s second attempt, Nandhikonda and Begaye synthesized a more refined matrix of nine dyes, with five of those exhibiting dual fluorescence.

"A lot of credit goes to Prem Nandhikonda. His tireless efforts really facilitated in getting this work out and into print," Heagy said.
“We developed a photophysical model to predict dual fluorescence,” Heagy said. “If you can predict dual fluorescence, you’ll save a lot of time and energy. We don’t use the shotgun approach; we’re looking for the silver bullet approach.”

This graphic explains the chemical properties that predict a dual-fluorescent dye. A seesaw balanced photophysical model is used to balance the dyes' electronic properties by directing substituent groups on the dyes to the correct positions. Graphic by Prem Nandhikonda/New Mexico Tech

Dr. Robert Strongin of Portland State University develops new dyes for biomedical use. In the Highlights article, he was quoted as saying that Heagy’s work represents “a breakthrough that will allow better understanding of fluorophore properties and enable the design of improved optical materials.”

The “shotgun approach” would be synthesizing a large library of 50 or more compounds. Heagy’s “silver bullet approach” involves identifying the characteristics common to dual fluorescent dyes.

As noted in the title of the paper in Chemical Communications, Heagy compares the predictive factor to balancing a seesaw.

“Through synthesis, we can ‘decorate’ a dye with different functional groups,” he said. “We’re looking for two molecular occupants that should be balanced. Most dyes have one predominant excited state and we’re designing them with two excited states. There has to be chemical equilibrium between those excited states.”

To be more specific, Heagy has found that a trait similar to most dual fluorescent dyes is that both excited states have similar energy but different geometry. One rotamer, or rotational isomer, of the molecule typically emits short-wavelength fluorescence and the other end emits long-wavelength fluorescence.

In the lab, Heagy and his students are looking for simple methods of producing these dyes and simple methods of testing them. He is looking for dyes that can be synthesized in as few as three steps (while some synthetic processes require up to 15 steps, or more).

Also, to test dyes, Heagy uses only a spectrofluorimeter – no expensive lasers or synchronized ultrafast pulses are required.
The applications for dual fluorescent dyes are wide ranging, but the two main uses would be in biomedical diagnosis and energy applications, like biofuels from microalgae and solar power, Heagy said.

Functional dyes are effective in biomedical research because they can adhere or bond to analytes that have no color, allowing researchers to track the movements of ions or biomolecules.

One of Heagy’s previous goals has been the development of dyes that attach to sugars, allowing diabetics to be able to monitor their blood-sugar levels in real time.

“For diabetics, that would be a real advent of technology,” he said. “Instead of pinpricks throughout the day, one could develop a continuous, real-time monitor of blood glucose. That’s a big goal for biotechnology.”